VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo - PubMed (original) (raw)

doi: 10.1038/nm1003. Epub 2004 Feb 22.

David Bebbington, Jeff Moore, Richele K Rasmussen, Abi O Ajose-Adeogun, Tomoko Nakayama, Joanne A Graham, Cecile Demur, Thierry Hercend, Anita Diu-Hercend, Michael Su, Julian M C Golec, Karen M Miller

Affiliations

• PMID: 14981513
• DOI: 10.1038/nm1003

Free article

VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo

Elizabeth A Harrington et al. Nat Med. 2004 Mar.

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Erratum in

• Nat Med. 2007 Apr;13(4):511

Abstract

The Aurora kinases are essential for the regulation of chromosome segregation and cytokinesis during mitosis. Aberrant expression and activity of these kinases occur in a wide range of human tumors, and lead to aneuploidy and tumorigenesis. Here we report the discovery of a highly potent and selective small-molecule inhibitor of Aurora kinases, VX-680, that blocks cell-cycle progression and induces apoptosis in a diverse range of human tumor types. This compound causes profound inhibition of tumor growth in a variety of in vivo xenograft models, leading to regression of leukemia, colon and pancreatic tumors at well-tolerated doses. Our data indicate that Aurora kinase inhibition provides a new approach for the treatment of multiple human malignancies.

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Comment in

• Aurora kinases dawn as cancer drug targets.
  Sausville EA. Sausville EA. Nat Med. 2004 Mar;10(3):234-5. doi: 10.1038/nm0304-234. Nat Med. 2004. PMID: 14991042 No abstract available.

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